TACC1 protein is rich in serine, proline, and acidic residues, has a 20-amino acid N terminus rich in tryptophan, contains 2 nuclear localization signals but no DNA- or RNA-binding domains, and has a 200-residue C terminus with extensive alpha-helical segments expected to adopt a coiled-coil structure. Northern blot analysis detected a major 8.0-kb TACC1 transcript in all tissues tested, with relatively weak expression in liver and lung. Introduction of TACC1 into stable cell lines resulted in morphologic changes consistent with a transformed phenotype and in anchorage-independent growth.
NCBI Summary:
This gene encodes a member of the transforming acidic colied-coil protein family. The encoded protein is a motor spindle protein that may play a role in stabilization of the mitotic spindle. This protein may also play a role in growth a differentiation of certain cancer cells. [provided by RefSeq, Nov 2011]
General function
Oncogenesis
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Cellular localization
Nuclear
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Ovarian function
Oogenesis, Oocyte maturation, Early embryo development
Comment
KIF2A regulates the spindle assembly and the metaphase I-anaphase I transition in mouse oocyte. Chen MH et al. (2016) KIF2A, a member of the kinesin-13 family, has been reported to play a role in spindle assembly in mitosis. However, its function in mammalian meiosis remains unknown. In this research, we examined the expression, localization and function of KIF2A during mouse oocyte meiosis. KIF2A was expressed in some key stages in mouse oocyte meiosis. Immunofluorescent staining showed that KIF2A distributed in the germinal vesicle at the germinal vesicle stage and as the spindle assembling after meiosis resumption, KIF2A gradually accumulated to the entire spindle. The treatment of oocytes with taxol and nocodazole demonstrated that KIF2A was co-localized with α-tubulin. Depletion of KIF2A by specific short interfering (si) RNA injection resulted in abnormal spindle assembly, failure of spindle migration, misaligned chromosomes and asymmetric cell division. Meanwhile, SKA1 expression level was decreased and the TACC3 localization was disrupted. Moreover, depletion of KIF2A disrupted the actin cap formation, arrested oocytes at metaphase I with spindle assembly checkpoint protein BubR1 activated and finally reduced the rate of the first polar body extrusion. Our data indicate that KIF2A regulates the spindle assembly, asymmetric cytokinesis and the metaphase I-anaphase I transition in mouse oocyte.//////////////////
TACC3 Is Important for Correct Progression of Meiosis in Bovine Oocytes. Mahdipour M et al. (2015) Transforming acidic coiled-coil (TACC) proteins are key players during mitosis via stabilization of the spindle. The roles of TACCs during meiosis are however less clear. We used bovine oocytes to study the expression and function of TACC3 during meiosis. TACC3 mRNA was detected in bovine oocytes during meiosis using qRT-PCR, and while it was also expressed in cleavage stage embryos, its expression was down-regulated at the morula and blastocyst stages. Immunofluorescence was used to demonstrate that TACC3 co-localized with tubulin in the metaphase I and II spindles. However, TACC3 was not detected at anaphase or telophase of the first meiotic division. Aurora A, which is known to phosphorylate and activate TACC3 in mitotic cells, showed a similar pattern of gene expression to that of TACC3 in meiotic oocytes and preimplantation embryos. Aurora A protein was however only very transiently associated to the meiotic spindle. Pharmaceutical inhibition of Aurora A activity inhibited TACC3 phosphorylation but did not prevent TACC3 appearance in the spindle. Inhibiting Aurora A activity did however lead to abnormal meiotic spindle formation and impaired maturation of bovine oocytes. Similar results were obtained by knock-down of TACC3 expression using siRNA injection. These results suggest that TACC3 is important for stabilizing the meiotic spindle, but phosphorylation of TACC3 by Aurora A is not required for its recruitment to the meiotic spindle although phosphorylation of TACC3 by other kinases cannot be excluded.//////////////////
Proteomic profiling of murine oocyte maturation. Vitale AM et al. In an effort to better understand oocyte function, we utilized two-dimensional (2D) electrophoresis and mass spectrometry to identify proteins that are differentially expressed during murine oocyte maturation. Proteins from 500 germinal vesicle (GV) and metaphase II-(MII) arrested oocytes were extracted, resolved on 2D electrophoretic gels, and stained with silver. Analysis of the gels indicated that 12 proteins appeared to be differentially expressed between the GV and MII stage. These proteins were then cored from the 2D gels and identified by mass spectrometry as: transforming acidic coiled-coil protein 3 (TACC3), heat shock protein 105 (HSP105), programmed cell death six-interacting protein (PDCD6IP), stress-inducible phosphoprotein (STI1), importin alpha2, adenylsuccinate synthase (ADDS), nudix, spindlin, lipocalin, lysozyme, translationally controlled tumor protein (TCTP), and nucleoplasmin 2 (NPM2). Interestingly, PDCD6IP, importin alpha2, spindlin, and NPM2 appear slightly larger in mass and more acidic on the MII oocyte gel compared to the GV oocyte gel, suggesting that they may be post-translationally modified during oocyte maturation. Given NPM2 is an oocyte-restricted protein, we chose to further investigate its properties during oocyte maturation and preimplantation development. Real-Time RT-PCR showed that NPM2 mRNA levels rapidly decline at fertilization. Indirect immunofluorescence analysis showed that, with the exception of cortical localization in MII-arrested oocytes, NPM2 is localized to the nucleus of both GV stage oocytes and all stages of preimplantation embryos. We then performed one-dimensional (1D) western blot analysis of mouse oocytes and preimplantation embryos and found that, as implicated by the 2D gel comparison, NPM2 undergoes a phosphatase-sensitive electrophoretic mobility shift during the GV to MII transition. The slower migrating NPM2 form is also present in pronuclear embryos but by the two-cell stage, the majority of NPM2 exists as the faster migrating form, which persists to the blastocyst stage. Mol. Reprod. Dev. (c) 2006 Wiley-Liss, Inc.
Expression regulated by
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Ovarian localization
Oocyte
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Meiotic regulation of TPX2 protein levels governs cell cycle progression in mouse oocytes. Brunet S et al. Formation of female gametes requires acentriolar spindle assembly during meiosis. Mitotic spindles organize from centrosomes and via local activation of the RanGTPase on chromosomes. Vertebrate oocytes present a RanGTP gradient centred on chromatin at all stages of meiotic maturation. However, this gradient is dispensable for assembly of the first meiotic spindle. To understand this meiosis I peculiarity, we studied TPX2, a Ran target, in mouse oocytes. Strikingly, TPX2 activity is controlled at the protein level through its accumulation from meiosis I to II. By RNAi depletion and live imaging, we show that TPX2 is required for spindle assembly via two distinct functions. It controls microtubule assembly and spindle pole integrity via the phosphorylation of TACC3, a regulator of MTOCs activity. We show that meiotic spindle formation in vivo depends on the regulation of at least a target of Ran, TPX2, rather than on the regulation of the RanGTP gradient itself.
Hao ZL,et al 202 reported TACC3 expression and localization in the murine egg and ovary.
A protein spot cored from a silver-stained two dimensional (2D) gel of
germinal vesicle stage immature mouse oocytes was identified as Transforming
Acidic Coiled Coil containing protein (TACC3) by tandem mass spectrometry. PCR
amplification revealed two alternatively spliced forms, Tacc3a and Tacc3b, in
mouse ovarian cDNA libraries. TACC3a encoded a 630 aa protein with a predicted
mass of 70 kDa. It contained seven 24 aa repeats at the N-terminus and two
coiled-coil domains at the C-terminus. TACC3b encoded a 426 aa protein with a
predicted mass of 49 kDa also containing two coiled coil domains, but lacking
the 168 aa repeat region. In addition to homology to the TACC family members,
murine TACC3 also showed 35.7% identity to the Xenopus protein, Maskin, a
cytoplasmic polyadenylation element binding protein (CPEB)-associated factor.
Northern blot analysis demonstrated that TACC3a is abundantly expressed in
adult testis and spleen and is moderately expressed in the ovary, heart, and
lung, suggesting a wide tissue distribution. Both myc-tagged TACC3a and TACC3b
targeted to the cytoplasm of transiently transfected CV-1 cells. In situ
hybridization of mouse ovarian tissue sections displayed abundant expression
of TACC3 specifically in the cytoplasm of growing oocytes, but not in
primordial or atretic follicles. This pattern of expression suggests that
TACC3 is expressed in ovarian cells undergoing active growth and development.